This list highlights key pediatric information from the studies submitted in response to pediatric legislative initiatives. CBER regulated products have an asterisk (*) by the proper name. To obtain all the information for a pediatric labeling change, select the pediatric labeling date in the first column of the database to reveal the additional information. To view all records in the database, select the All button at the bottom of the page. To search for a specific pediatric labeling change, enter the trade name or generic name in the Filter box and select Show Items. Note: CBER and CDER regulated biologics with pediatric labeling changes before 9/27/2007 are excluded from the database.

* Use in 12 – 18 years is supported by evidence from adequate and well controlled studies in adults with additional safety and PK data from an open label trial in 22 adolescents 12 years and older exposed to Naftin Gel at a dose of approximately 4 g/day * Safety and effectiveness in pediatric patients less than12 years have not been established * Adverse reactions were similar to those observed in adults * Postmarketing study

* Multi-center, randomized, double-blind, placebo-controlled, flexible-dose trial in 308 adolescents 12 – 17 years failed to demonstrate efficacy * Emsam should not be used in patients less than 18 years. * Use in patients less than 12 years is contraindicated because of the potential for a hypertensive crisis, which may be increased compared to adolescents and adults based on limited PK data suggesting higher exposure even at the lowest dose * Adverse events were similar to those observed in adults * Postmarketing study

* Use was evaluated in a 16 week double-masked, randomized, vehicle controlled study in pediatric patients with several different conditions (post-chemotherapy, alopecia areata, and adolescents with hypotrichosis and no associated medical condition *No new safety issues were observed * Postmarketing study

*Expanded the indication from adults to pediatric patients 12 – 17 years * Safety and effectiveness have not been established in pediatric patients less than 12 years * In a trial to evaluate the effect on HPA axis suppression in pediatric patients 12 – 17 years, adrenal suppression was identified in 1 of 30 patients (3.3%) after 4 weeks of treatment * Rare systemic toxicities such as Cushing’s syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in pediatric patients, especially those with prolonged exposure to large doses of high potency topical corticosteroids *Local adverse reactions including striae have also been reported with use of topical corticosteroids in pediatric patients * Information on dose and maximum weekly dose, adverse reactions, and clinical trials * Postmarketing study

* Approved for use in adults and pediatric patients 12 years and older * Safety and efficacy in pediatric patients younger than 12 years have not been established * Orally inhaled corticosteroids may cause a reduction in growth velocity when administered to children and adolescents. The growth of children and adolescents receiving orally inhaled corticosteroids, including Arnuity Ellipta, should be monitored routinely. The potential growth effects of prolonged treatment should be weighed against the clinical benefits obtained and the risks associated with alternative therapies * Information on safety, adverse events and clinical trials * New dosage form

* Safety and effectiveness in pediatric patients 12 years and older have been established based on PK data in adults and adolescents using Keppra XR and efficacy and safety data in pediatric studies using immediate-release Keppra * Safety and effectiveness of in patients below the age of 12 years have not been established * Information on PK parameters and PK study *Postmarketing study

*The safety and effectiveness of memantine have not been established in pediatric patients *Memantine failed to demonstrate efficacy in two 12-week controlled clinical studies of 578 pediatric patients aged 6-12 years with autism spectrum disorders *Adverse reactions were similar to those observed in adults* Information on dosing, adverse reactions, clinical trials

*Efficacy for the maintenance treatment of irritability associated with autistic disorder was not established in a 12 week clinical trial in 85 pediatric patients 6-17 years * Information on clinical trial* Postmarketing study

*Reyataz oral powder approved for use in pediatric patients at least 3 months and between 10 kg to less than 25 kg; capsule previously approved in 6 years and older* Not recommended in pediatric patients less than 3 months because of the risk of kernicterus* Reyataz oral powder contains phenylalanine which can be harmful to patients with phenylketonuria * Adverse reactions were similar to those observed in adults* Oral powder must be mixed with food or beverage for administration and ritonavir must be given immediately afterwards * Information on mixing oral powder with food such as appleasauce or yogurt or milk, water or infant formula * Information on dosing in patients at least 3 months and weighing between 10 to less than 25kg, adverse reactions, laboratory abnormalities, PK parameters, and clinical trials* New dosage form

Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) and postoperative nausea and vomiting (PONV)

Chemotherapy-Induced Nausea and Vomiting *Approved for prevention of acute CINV in 1 month - < 17 years* Safety and effectiveness in neonates less than 1 month of age have not been established* Pediatric patients require a higher palonosetron dose than adults (20 mcg/kg with max of 1.5 mg x 1 vs 0.25 mg x 1 *Adverse reactions were similar to those observed in adults *Information on dosing, PK parameters, clinical trial, adverse reactions Postoperative Nausea and Vomiting Studies *Safety and efficacy have not been established in pediatric patients for PONV *Adverse reactions were similar to those observed in adults* Information on dosing, clinical trials

*Approved for use in pediatric patients 12 years and older based on clinical trials conducted with mesalamine 400 mg delayed release tablets which is approved in 5-17 years* Delzicol is bioequivalent to the mesalamine delayed-release tablets *There is no age appropriate Delzicol formulation available for patients less than 12 years *Safety and effectiveness of Delzicol in the maintenance of remission of ulcerative colitis in pediatric patients have not been established *Information on dosing* New dosage form

*Approved for use in adults and pediatric patients 12 years and older *Safety and efficacy hav not been established in children less than 12 years *The growth of pediatric patients receiving orally inhaled corticosteroids should be monitored routinely *To minimize the systemic effects of orally inhaled corticosteroids each patient should be titrated to his/her lowest effective dose *Information on dosing, adverse reactions, and clinical trials *New dosage form

* Expanded indication to include 1 month to 4 years; previously approved for use in 4 years and older * Safety and effectiveness have not been established in neonates * Adversereactions observed in pediatric patients 1 month – 6 years were similar to adults except for an increased incidence of low Phe levels. 25% (16/65) experienced low Phe for age * Information on adding crushed tablet or powder for oral solution to small amounts of soft food such as apple sauce* Information on dosing, adverse reactions, PK parameters, and clinical trials

* Approved for the treatment of CIU in adults and pediatric patients 12 years and older who remain symptomatic despite H1 antihistamine treatment * Clinical studies with Xolair have not been conducted in CIU patients less than 12 years. Considering the risk of anaphylaxis and malignancy seen in Xolair-treated patients 12 years and older, the use of Xolair in patients less than 12 years is not recommended * Dosing in CIU is not based on serum IgE level or body weight * Adverse reactions in adolescents and adults were similar and include miscellaneous infections, arthralgias, headache, nausea, and cough * Information on adverse reactions, dosing, and clinical trials in adults and pediatric patients 12 years and older

* Approved for use in pediatric patients 2 years and older * Safety and effectiveness have not been established in pediatric patients less than 2 years. Use in this age group has not been evaluated because treatment of HBV in this age group is rarely required * There are limited data available on the use of Baraclude in lamivudine-experienced pediatric patients * Adverse reactions in clinical trials were similar to those observed in adults * Information on dosing in pediatric patients 2 years and weighing at least 10 kg, adverse reactions, PK parameters and clinical trials * New dosage form

*Labeling updated to include information on results of an open-label pediatric safety extension study* During the study, there were 42 deaths with 37 of these deaths reported prior to a decision to titrate patients to a lower dosage because of a finding of increased mortality. An increase in mortality was observed with increasing doses *Causes of death in the extension study were typical of patients with PAH

* Expanded indication to include 6 years to less than 12 years; previously approved for use in 12 years and older *Safety and effectiveness in pediatric patients less than 6 years of age have not been established *Adverse reactions similar to those observed in adults* Information on dose, and clinical trial

*Packet for oral suspension: Approved for use in infants 4 weeks and older, weighing at least 3 kg to < 20 kg. Chewable tablet previously approved down to 2 years* Safety and dosing information have not been established in infants less than 4 weeks *Adverse reactions similar to those observed in adults* Information on dosing,clinical trial and PK parameters*Information on preparation of a suspension*New dosage form

*The safety and effectiveness in pediatric patients have not been established *No clinical benefit was demonstrated in 2 single arm trials in pediatric patients* The adverse reaction (AR) profile was consistent with the known AR profile in adults, with the exception of laboratory abnormalities which occurred more commonly in pediatric patients* Information on dosing, adverse reactions, and clinical trials

Prophylaxis of invasive Aspergillus and Candida infections in high risk patients

*Safety and effectiveness have been established in pediatric patients 13 - 17 years. Use is supported by evidence from adequate and well-controlled studies in adults. PK and safety in pediatric patients 13 - 17 years were also assessed and are similar to adults.* Safety and effectiveness in pediatric patients less than 13 years have not been established* Information on dosing, PK, and clinical trials

*Efficacy in the pediatric population was established based on adult trials and supported by a dose-ranging trial and an open label trial that achieved adequate mean arterial pressure control in pediatric patients *No novel safety issues were found in these two studies. *Information on dosing, PK parameters and clinical trials

*Approved as adjunctive therapy for pediatric patients 10 years and older with rCPS for whom the potential benefits outweigh the risk of vision loss. Sabril is not a first line agent for rCPS * Safety and effectiveness for pediatric patients less than 10 years with refractory rCPS have not been established *Pooled data from 3 controlled trials in pediatric patients demonstrated that 6% (10/165) of Sabril patients experienced somnolence compared to 5% (5/104) of placebo patients. In those same studies, 10% (17/165) of Sabril patients experienced fatigue compared to 7% (7/104) of placebo patients; 47% (77/163) of Sabril patients versus 19% (19/102) of placebo patients gained greater than or equal to 7% of baseline body weight *Adverse reactions (ARs) in the pediatric population were similar to those reported in adults. Overall, ARs in pediatric patients 10-16 years included increased weight, upper respiratory tract infection, tremor, fatigue, aggression and diplopia *Information on weight based dosing, dosing in renal impairment, safety information and clinical trials

*Safety and effectiveness of Asacol HD in pediatric patients have not been established *Since studies were performed in Asacol rather than Asocol HD, information added to labeling referring reader to prescribing information for other approved mesalamine products for the safety and effectiveness of these products in pediatric patients

*Safety and effectiveness in pediatric patients 5 - 17 years have been established over a 6-week period. Use in this age group is supported by evidence from studies in adults and 1 study in pediatric patients*Safety and effectiveness in pediatric patients below 5 years have not been established*Safety and effectiveness for the maintenance of remission of ulcerative colitis in pediatric patients have not been established*Adverse reactions in the pediatric population were similar to those reported in adults*Information on dose, adverse reactions, PK and clinical trials*Postmarketing study

For adults, adolescents, and children with hemophilia A for (1) the control and prevention of bleeding episodes, (2) perioperative management, and (3) routine prophylaxis to prevent or reduce the frequency of bleeding episodes.

*Expanded the indication to pediatric patients down to 6 years; previously approved in pediatric patients 12 years and older *Safety and effectiveness in pediatric patients < 6 years have not been established *Information on dosing, clinical trial, and adverse reactions *Postmarketing study"

"*Indicated in combination with other antiretroviral agents in adults and children aged 12 years and older and weighing at least 40 kg *Not recommended in pediatric patients <12 years or weighing < 40 kg *Safety and efficacy have not been established in pediatric patients who are integrase strand transfer ibitor (INSTI)-experienced with documented or clinically suspected resistance to other INSTIs (raltegravir, elvitegravir) *The safety, virologic, and unologic were evaluated in 23 treatment-experienced, INSTI-naïve, HIV-1 infected patients aged 12 - < 18 years in an open-label, multicenter, dose-finding clinical trial *Adverse reactions were similar to those observed in adults * Information on dosing, clinical trial, and PK *New drug

"*Expanded the indication from adults to pediatric patient 10-17 years *Safety and efficacy for treatment resistant depression in patients < 18 years have not been established *Symbyax is not approved for any indication in patients < 10 years *In a placebo-controlled clinical trial in patients 10 to 17 years, somnolence-related adverse events were commonly reported with drug treatment occurring in 23.5% of drug-treated patients compared with 2.4% of placebo-treated patients *The types of adverse reactions observed with olanzapine and fluoxetine hydrochloride in children and adolescents were similar to adult but the magnitude and frequency of some changes were greater in children and adolescents than adults. These included increases in lipids, hepatic enzymes, and prolactin, and increases in the QT interval. The frequency of weight gain greater than or equal to 7%, and the magnitude and frequency of increases in lipids, hepatic analytes, and prolactin in children and adolescents treated with olanzapine and fluoxetine hydrochloride were similar to those observed in adolescents treated with olanzapine monotherapy *Overall, 14.1% of the 170 patients in the olanzapine and fluoxetine hydrochloride group discontinued due to adverse reactions compared with 5.9% of the 85 patients for placebo. Adverse reactions leading to discontinuation associated with the use of olanzapine and fluoxetine hydrochloride were weight increased (2.9%), suicidal ideation (1.8%), bipolar disorder (1.2%), and somnolence (1.2%) versus placebo patients which had 0% incidence of weight increased, bipolar disorder, and somnolence, and a 1.2% incidence of suicidal ideation *Information on dosing, clinical trial, and adverse reactions

*Safety and effectiveness in pediatric patients 4 months and older have been demonstrated based on the evidence from adequate and well-controlled studies in adult and pediatric patients and additional pediatric pharmacokinetic and safety data*Safety and effectiveness in pediatric patients < 4 months have not been established*In all pediatric studies with Mycamine, 439/479 (92%) patients experienced at least one treatment-emergent adverse reaction. Gastrointestinal symptoms including vomiting, diarrhea, nausea, abdominal pain, and abdominal distension occurred in 285 pediatric patients (60%)*Information on population PK, dosing, adverse reactions, and clinical trials *Postmarketing study

Loading and maintenance infusion for sedation in intubated and mechanically ventilated pediatric patients

*Safety and efficacy have not been established for procedural or ICU sedation in pediatric patients *One assessor-blinded trial in pediatric patients and two open label studies in neonates were conducted to assess efficacy for ICU sedation. These studies did not meet their primary efficacy endpoints and the safety data submitted were insufficient to fully characterize the safety profile of dexmedetomidine for this patient population *Use for procedural sedation in pediatric patients has not been evaluated

Reversal of the effects of non-depolarizing neuromuscular-blocking agents after surgery

"*Approved for use in pediatric patients of all ages *The evidence for efficacy of neostigmine is derived from the published literature * Recovery of neuromuscular activity occurs more rapidly with smaller doses of cholinesterase inhibitors in infants and children than in adults. However, infants and small children may be at greater risk of complications from incomplete reversal of neuromuscular blockade due to decreased respiratory reserve. The risks associated with incomplete reversal outweigh any risk from giving higher doses of neostigmine *Since the blood pressure in pediatric patients, particularly infants and neonates is sensitive to changes in heart rate, the effects of an anticholinergic agent (e.g., atropine) should be observed prior to administration of neostigmine to lessen the probability of bradycardia and hypotension *Information on dose, and pk *New drug

* Labeling updated with dosing recommendations for pediatric patients 3 months - 3 years and weighing at least 3.5 kg * Use in pediatric patients < 3 months OR less than 3.5 kg body weight is not recommended because the safety, pharmacokinetics, and antiviral activity have not been evaluated and there is a risk of developing HIV resistance if efavirenz is underdosed.* Information on population PK, safety, virologic, and immunologic response from 3 open-label clinical trials in patients 3 months - 21 years.* Postmarketing study

* Efficacy was not established in an 8-week placebo-controlled monotherapy trial of Seroquel XR in children and adolescents 10-17 years with bipolar depression.* In the same study patients treated with Seroquel XR exhibited metabolic changes, weight gain, and increases in blood pressure and heart rate.* The most commonly observed adverse reactions were dizziness 7%, diarrhea 5%, fatigue 5% and nausea 5% * Information on adverse reactions, clinical tria * Postmarketing study

*Approved for the maintenance treatment of ADHD in pediatric patients 6-17 years * Information on one short term efficacy trial and one maintenance trial in pediatric patients 6-17 years * New indication

Products in this table are listed by labeling change date in descending order and fell within the scope of the Pediatric Rule, the Best Pharmaceuticals for Children Act (BPCA), and the Pediatric Research Equity Act (PREA), and contain new pediatric information. All other labeling changes are based on information from clinical trials in pediatric patients. This list only serves to highlight key information affecting the pediatric population at the time the particular application was approved resulting from the studies performed for the Pediatric Rule, BPCA and PREA.